We present theoretical and experimental arguments supporting the hypot
hesis that the cell surface glycocalyx may negatively regulate adhesiv
e phenomena. First, it is recalled that a repulsive interaction of sev
eral thousands of piconewtons may be generated on a contact area of ab
out 1/100 mu m(2) by a combination of electrostatic and entropic force
s (steric stabilization). Second, electron microscopical data are repo
rted to provide an estimate of the thickness of the cell coats of muri
ne macrophages and sheep erythrocytes made phagocytable by exposure to
glutaraldehyde or specific antibodies. Using conventional carbohydrat
e staining procedures, it is shown that the total thickness of the ele
ctron-dark regions in areas of intercellular contact is lower than the
sum of the thicknesses of electron-dark regions on free cell areas. F
urther, removing negative charges with neuraminidase or neutralizing t
hese charges with polylysine may reduce intermembrane distance in cont
act areas. Third, it is shown that a decrease of erythrocyte surface c
harges with neuraminidase increases their adhesion to murine phagocyte
s under dynamic, not static conditions. It is concluded that a major d
eterminant of steric stabilization is the relative length of adhesion
molecules and surface repeller elements, and that repulsion is particu
larly important under dynamic conditions. Thus, dynamic effects must b
e included in models of steric stabilization.